2021/09/28 by Judith G. Levin, Alan Rein · 1 voice
Immunology and Microbiology · Medicine · Biochemistry, Genetics and Molecular Biology · #HIV Research and Treatment #HIV/AIDS drug development and treatment #RNA and protein synthesis mechanisms
paper · doi:10.1073/pnas.2115344118
openalex publication_date 2021/09/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
AIDS is caused by HIV-1. HIV-1 is a member of the retrovirus family; like all retroviruses, the virus particle is roughly spherical and about 100 to 120 nm in diameter. It is assembled in the virus-producing cell from virus-coded proteins and of course, packages the viral genome, so that the necessary genetic information can be passed on to the next generation of viruses. Retroviruses are distinctive in that the genetic information in the virus particle is single-stranded RNA, but when they infect a new host cell, the RNA is copied into double-stranded DNA by reverse transcriptase, the virus-coded polymerase present in the particle. This viral DNA is subsequently inserted into the host chromosomal DNA, where it will remain for the lifetime of the cell. The DNA copy of the viral genetic information is then transcribed and translated by the cellular gene expression machinery (1). This scenario implies, in turn, that RNA copies of the genome have two distinct functions in the virus-producing cell. First, they are the messenger RNAs (mRNAs) for the virus-coded proteins, and second, they are the RNA molecules to be packaged into the assembling, nascent virus particles. In fact, full-length (∼9.7-kb) RNAs are the mRNA for the major building block of progeny virus particles (the “Gag” polyprotein) and for an extended protein containing both Gag and the virus-coded enzymes. The mechanism for distinguishing these two functional classes of genomic RNA (gRNA) molecules has been under investigation for nearly 50 y. In 1974 (before the appearance of HIV), it was reported that treatment of murine leukemia virus (MLV)–infected cells with actinomycin D (a potent inhibitor of cellular and viral RNA synthesis) resulted in the production of particles that had all the characteristics of authentic MLV virions except that after brief exposure to the drug, the virions lacked gRNA … [↵][1]1To whom correspondence may be addressed. Email: levinjuatmail.nih.gov or reinaatmail.nih.gov. [1]: #xref-corresp-1-1